study of inotuzumab ozogamicin combined to chemotherapy in older patients with philadelphia chromosome-negative cd22+ b-cell precursor all

Conditions: Acute Lymphoblastic Leukemia (ALL) - Philadelphia Chromosome (Ph)-Negative CD22+ B-cell Precursor (BCP)

Summary: the aim of the present ewall-ino study is to confirm very promising results obtained with a combination of ino and mild chemotherapy in older de novo cd22+ b-all patients. for that purpose, safety and efficacy of a weekly ino administration combined to mild-intensity chemotherapy will be evaluated in a cohort of patients aged more than 55 years with newly diagnosed previously untreated ph-negative (cd22+) bcp-all. conversely to the mdacc minihcvd-ino study and in order to lower the overall toxicity of the combination, ino will be given as part of the remission induction treatment phase during the first 2 treatment cycles only, in combination with corticosteroid, vincristine, cyclophosphamide and intrathecal prophylaxis only; then, all responding patients will received standard ino-free chemotherapy as consolidation and maintenance.

ino schedule of administration will be as described in the refractory/relapsed ino-vate study for the first cycle, with sequential day 1/8/15 doses of 0.8, 0.5 and 0.5 mg/m2, respectively. reduced dose of ino will be used for the second and last cycle (0.5 mg/m2 on day 1/8). this was retained in order: 1. to minimize potential toxicities, including liver disorders and prolonged thrombocytopenia; and 2. to allow delivery of subsequent chemotherapy consolidations cycles.

Eligibility criteria:
inclusion criteria: * patients aged more than 55 years old, * with confirmed diagnosis of bcp-all according to world health organisation (who) criteria expressing the cd22 antigen by flow cytometry (20% or more positive blast cells), * without central nervous system (cns) involvement, * without bcr-abl fusion by standard cytogenetics, fluorescence in situ hybridization (fish) analysis and/or rt-pcr, * previously untreated, * eligible to intensive chemotherapy, due to general health status, * ecog performance status ≤ 2, * patients must have the following laboratory values unless considered due to leukemia: ast and alt ≤ 2.5 x upper the limit of normal (uln); estimated gfr ≥ 50 ml/min using the mdrd equation; total and direct serum bilirubin ≤ 1.5 x uln; electrolyte panel within normal ranges for the institution unless attributed to the underlying disease. * written informed consent obtained prior to any screening procedures. * eligible for national health insurance in france. exclusion criteria: * concurrent therapy with any other investigational agent or cytotoxic drug, * prior documented chronic liver disease, * active hepatitis b virus (hbv) or hepatitis c virus (hcv) or positive hiv serology, * female patients who are pregnant or breast feeding or patients of childbearing potential not willing to use a double barrier method of contraception during the study and for 3 months following the last dose of maintenance. * male patients whose sexual partner(s) are women of childbearing potential who are not willing to use a double barrier method of contraception, one of which includes a condom, during the study and for 3 months following the last dose of maintenance. * any of concurrent severe and/or uncontrolled medical condition, which could compromise participation in the study.